tbuckley/cabot-search huggingface dataset:
Alox15/15-HpETE Aggravates Myocardial Ischemia-Reperfusion Injury by Promoting Cardiomyocyte Ferroptosis
Authors: Wenbin Cai, Le Liu, Xuelian Shi, Yanan Liu, Jin Wang, Xuan Fang, Zhipeng Chen, Ding Ai, Yi Zhu, Xu Zhang
Journal: Circulation (2023)

Myocardial ischemia-reperfusion (I/R) injury causes cardiac dysfunction to myocardial cell loss and fibrosis. Prevention of cell death is important to protect cardiac function after I/R injury. The process of reperfusion can lead to multiple types of cardiomyocyte death, including necrosis, apoptosis, autophagy, and ferroptosis. However, the time point at which the various modes of cell death occur after reperfusion injury and the mechanisms underlying ferroptosis regulation in cardiomyocytes are still unclear.Using a left anterior descending coronary artery ligation mouse model, we sought to investigate the time point at which the various modes of cell death occur after reperfusion injury. To discover the key molecules involved in cardiomyocyte ferroptosis, we performed a metabolomics study. Loss/gain-of-function approaches were used to understand the role of 15-lipoxygenase (Alox15) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α) in myocardial I/R injury.We found that apoptosis and necrosis occurred in the early phase of I/R injury, and that ferroptosis was the predominant form of cell death during the prolonged reperfusion. Metabolomic profiling of eicosanoids revealed that Alox15 metabolites accumulated in ferroptotic cardiomyocytes. We demonstrated that Alox15 expression was specifically increased in the injured area of the left ventricle below the suture and colocalized with cardiomyocytes. Furthermore, myocardial-specific knockout of Alox15 in mice alleviated I/R injury and restored cardiac function. 15-Hydroperoxyeicosatetraenoic acid (15-HpETE), an intermediate metabolite derived from arachidonic acid by Alox15, was identified as a trigger for cardiomyocyte ferroptosis. We explored the mechanism underlying its effects and found that 15-HpETE promoted the binding of Pgc1α to the ubiquitin ligase ring finger protein 34, leading to its ubiquitin-dependent degradation. Consequently, attenuated mitochondrial biogenesis and abnormal mitochondrial morphology were observed. ML351, a specific inhibitor of Alox15, increased the protein level of Pgc1α, inhibited cardiomyocyte ferroptosis, protected the injured myocardium, and caused cardiac function recovery.Together, our results established that Alox15/15-HpETE-mediated cardiomyocyte ferroptosis plays an important role in prolonged I/R injury.
Comprehensive DNA Methylation Analysis Indicates That Pancreatic Intraepithelial Neoplasia Lesions Are Acinar-Derived and Epigenetically Primed for Carcinogenesis
Authors: Emily K.W. Lo, Brian M. Mears, H. Carlo Maurer, Adrian Idrizi, Kasper D. Hansen, Elizabeth D. Thompson, Ralph H. Hruban, Kenneth P. Olive, Andrew P. Feinberg
Journal: Cancer Research (2023)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is believed to arise from the accumulation of a series of somatic mutations and is also frequently associated with pancreatic intraepithelial neoplasia (PanIN) lesions. However, there is still debate as to whether the cell type-of-origin of PanINs and PDACs in humans is acinar or ductal. As cell type identity is maintained epigenetically, DNA methylation changes during pancreatic neoplasia can provide a compelling perspective to examine this question. Here, we performed laser-capture microdissection on surgically resected specimens from 18 patients to isolate, with high purity, DNA for whole-genome bisulfite sequencing from four relevant cell types: acini, nonneoplastic ducts, PanIN lesions, and PDAC lesions. Differentially methylated regions (DMR) were identified using two complementary analytical approaches: bsseq, which identifies any DMRs but is particularly useful for large block-like DMRs, and informME, which profiles the potential energy landscape across the genome and is particularly useful for identifying differential methylation entropy. Both global methylation profiles and block DMRs clearly implicated an acinar origin for PanINs. At the gene level, PanIN lesions exhibited an intermediate acinar-ductal phenotype resembling acinar-to-ductal metaplasia. In 97.6% of PanIN-specific DMRs, PanIN lesions had an intermediate methylation level between normal and PDAC, which suggests from an information theory perspective that PanIN lesions are epigenetically primed to progress to PDAC. Thus, epigenomic analysis complements histopathology to define molecular progression toward PDAC. The shared epigenetic lineage between PanIN and PDAC lesions could provide an opportunity for prevention by targeting aberrantly methylated progression-related genes. Significance: Analysis of DNA methylation landscapes provides insights into the cell-of-origin of PanIN lesions, clarifies the role of PanIN lesions as metaplastic precursors to human PDAC, and suggests potential targets for chemoprevention.
Effect of preoperative chemotherapy on the outcome of women with operable breast cancer
Authors: B Fisher, J Bryant, N Wolmark, E Mamounas, A Brown, E R Fisher, D L Wickerham, M Begovic, A DeCillis, A Robidoux, R G Margolese, A B Cruz, J L Hoehn, A W Lees, N V Dimitrov, H D Bear
Journal: Journal of Clinical Oncology (2023)

PURPOSE To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P &lt; .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.
Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys
Authors: Bai Xu, Dingyang Liu, Weiyuan Liu, Ge Long, Wenbin Liu, Yayu Wu, Xinghui He, Yeyu Shen, Peipei Jiang, Man Yin, Yongheng Fan, He Shen, Liyang Shi, Qi Zhang, Weiwei Xue, Chen Jin, Zhenni Chen, Bing Chen, Jiayin Li, Yali Hu, Xing Li, Zhifeng Xiao, Yannan Zhao, Jianwu Dai
Journal: Bioactive Materials (2023)

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.
Cesarean Delivery Uptake Trends Associated With Patient Features and Threshold for Labor Anomalies
Authors: Paolo Ivo Cavoretto, Massimo Candiani, Antonio Farina
Journal: JAMA Network Open (2023)

Anna M. Frappaolo, BA; Teresa C. Logue, MD, MPH; Dena Goffman, MD; Lisa M. Nathan, MD; Jean-Ju Sheen, MD; Maria Andrikopoulou, MD, PhD; Timothy Wen, MD, MPH; Mary E. D'Alton, MD; Alexander M. Friedman, MD, MPH
Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles
Authors: Yanmeng Yang, Yingnan Wu, Dahou Yang, Shu Hui Neo, Nurul Dinah Kadir, Doreen Goh, Jian Xiong Tan, Vinitha Denslin, Eng Hin Lee, Zheng Yang
Journal: Bioactive Materials (2023)

Secretome derived from mesenchymal stem cells (MSCs) have profound effects on tissue regeneration, which could become the basis of future MSCs therapies. Hypoxia, as the physiologic environment of MSCs, has great potential to enhance MSCs paracrine therapeutic effect. In our study, the paracrine effects of secretome derived from MSCs preconditioned in normoxia and hypoxia was compared through both in vitro functional assays and an in vivo rat osteochondral defect model. Specifically, the paracrine effect of total EVs were compared to that of soluble factors to characterize the predominant active components in the hypoxic secretome. We demonstrated that hypoxia conditioned medium, as well as the corresponding EVs, at a relatively low dosage, were efficient in promoting the repair of critical-sized osteochondral defects and mitigated the joint inflammation in a rat osteochondral defect model, relative to their normoxia counterpart. In vitro functional test shows enhancement through chondrocyte proliferation, migration, and matrix deposition, while inhibit IL-1β-induced chondrocytes senescence, inflammation, matrix degradation, and pro-inflammatory macrophage activity. Multiple functional proteins, as well as a change in EVs’ size profile, with enrichment of specific EV-miRNAs were detected with hypoxia preconditioning, implicating complex molecular pathways involved in hypoxia pre-conditioned MSCs secretome generated cartilage regeneration.
More Attention Should Be Paid to Less Severe Nonculprit Lesions
Authors: Shichu Liang, Min Ma, Yong He
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
CDC: <i>Candida auris</i> Fungal Infections and Drug Resistance on the Rise
Authors: Emily Harris
Journal: JAMA (2023)

The US maternal mortality rate continued to increase in 2021, according to a new report from the National Center for Health Statistics.The trend predated the COVID-19 pandemic: between 2018 and 2019, the rate increased from 17.4 maternal deaths per 100 000 live births to 20.1.It then continued to rise to 23.8 in 2020 and to 32.9 in 2021.There were 1205 maternal deaths in 2021 compared with 658 in 2018.Disparities in maternal mortality also persisted in 2021, with 69.9 Black women dying per 100 000 live births-a 2.6 times higher rate than that of White women that year.For all racial and ethnic groups included in the analysis-Black, Hispanic, and White-the number of deaths per 100 000 live births increased every year from 2018 through 2021.The maternal mortality rate also increased substantially for women aged 40 years or older between 2020 to 2021, from about 107.9 deaths per 100 000 live births to 138.5.In 2019, the maternal mortality rate for this age group was 75.5, a decrease from 81.9 the year prior.
Guiding Patients Through a “Watch-and-Wait” Approach for Rectal Cancer—Understanding the Functional Outcomes
Authors: Jennifer E. Hrabe, Muneera R. Kapadia
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
HHS Announces $25 Million to Expand School-Based Health Care
Authors: Emily Harris
Journal: JAMA (2023)

The US maternal mortality rate continued to increase in 2021, according to a new report from the National Center for Health Statistics.The trend predated the COVID-19 pandemic: between 2018 and 2019, the rate increased from 17.4 maternal deaths per 100 000 live births to 20.1.It then continued to rise to 23.8 in 2020 and to 32.9 in 2021.There were 1205 maternal deaths in 2021 compared with 658 in 2018.Disparities in maternal mortality also persisted in 2021, with 69.9 Black women dying per 100 000 live births-a 2.6 times higher rate than that of White women that year.For all racial and ethnic groups included in the analysis-Black, Hispanic, and White-the number of deaths per 100 000 live births increased every year from 2018 through 2021.The maternal mortality rate also increased substantially for women aged 40 years or older between 2020 to 2021, from about 107.9 deaths per 100 000 live births to 138.5.In 2019, the maternal mortality rate for this age group was 75.5, a decrease from 81.9 the year prior.
A translatome-transcriptome multi-omics gene regulatory network reveals the complicated functional landscape of maize
Authors: Wanchao Zhu, Xinxin Miao, Jia Qian, Sijia Chen, Qixiao Jin, Mingzhu Li, Linqian Han, Wanshun Zhong, Dan Xie, Xiaoyang Shang, Lin Li
Journal: Genome biology (2023)

Abstract Background Maize ( Zea mays L.) is one of the most important crops worldwide. Although sophisticated maize gene regulatory networks (GRNs) have been constructed for functional genomics and phenotypic dissection, a multi-omics GRN connecting the translatome and transcriptome is lacking, hampering our understanding and exploration of the maize regulatome. Results We collect spatio-temporal translatome and transcriptome data and systematically explore the landscape of gene transcription and translation across 33 tissues or developmental stages of maize. Using this comprehensive transcriptome and translatome atlas, we construct a multi-omics GRN integrating mRNAs and translated mRNAs, demonstrating that translatome-related GRNs outperform GRNs solely using transcriptomic data and inter-omics GRNs outperform intra-omics GRNs in most cases. With the aid of the multi-omics GRN, we reconcile some known regulatory networks. We identify a novel transcription factor, ZmGRF6 , which is associated with growth. Furthermore, we characterize a function related to drought response for the classic transcription factor ZmMYB31 . Conclusions Our findings provide insights into spatio-temporal changes across maize development at both the transcriptome and translatome levels. Multi-omics GRNs represent a useful resource for dissection of the regulatory mechanisms underlying phenotypic variation.
Mn-doped Ti-based MOFs for magnetic resonance imaging-guided synergistic microwave thermal and microwave dynamic therapy of liver cancer
Authors: Qiongyu Qin, Ming Yang, Yu Shi, Haijing Cui, Chunshu Pan, Wenzhi Ren, Aiguo Wu, Jianqing Hu
Journal: Bioactive Materials (2023)

Currently, precise ablation of tumors without damaging the surrounding normal tissue is still an urgent problem for clinical microwave therapy of liver cancer. Herein, we synthesized Mn-doped Ti MOFs (Mn-Ti MOFs) nanosheets by in-situ doping method and applied them for microwave therapy. Infrared thermal imaging results indicate Mn-Ti MOFs can rapidly increase the temperature of normal saline, attributing to the porous structure improving microwave-induced ion collision frequency. Moreover, Mn-Ti MOFs show higher 1O2 output than Ti MOFs under 2 W of low-power microwave irradiation due to the narrower band-gap after Mn doping. At the same time, Mn endows the MOFs with a desirable T1 contrast of magnetic resonance imaging (r2/r1 = 2.315). Further, results on HepG2 tumor-bearing mice prove that microwave-triggered Mn-Ti MOFs nearly eradicate the tumors after 14 days of treatment. Our study offers a promising sensitizer for synergistic microwave thermal and microwave dynamic therapy of liver cancer.
Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer
Authors: Cornelia Liedtke, Chafika Mazouni, Kenneth R. Hess, Fabrice André, Attila Tordai, Jaime A. Mejia, W. Fraser Symmans, Ana M. Gonzalez-Angulo, Bryan Hennessy, Marjorie Green, Massimo Cristofanilli, Gabriel N. Hortobagyi, Lajos Pusztai
Journal: Journal of Clinical Oncology (2023)

Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC.
Cesarean Delivery Trends Among Patients at Low Risk for Cesarean Delivery in the US, 2000-2019
Authors: Anna M. Frappaolo, Teresa C. Logue, Dena Goffman, Lisa M. Nathan, Jean-Ju Sheen, Maria Andrikopoulou, Timothy Wen, Mary E. D’Alton, Alexander M. Friedman
Journal: JAMA Network Open (2023)

Reducing rates of unnecessary cesarean deliveries is both a national and a global health objective. However, there are limited national US data on trends in indications for low-risk cesarean delivery.To determine temporal trends in and indications for cesarean delivery among patients at low risk for the procedure over a 20-year period.This cross-sectional study analyzed 2000 to 2019 delivery hospitalizations using the National Inpatient Sample. Births at low risk for cesarean delivery were identified using a definition from the Society for Maternal-Fetal Medicine and additional criteria. Temporal trends in cesarean birth were analyzed using joinpoint regression to estimate the average annual percentage change (AAPC) with 95% CIs. Data analysis was performed from August 2022 to January 2023.This analysis evaluated cesarean birth trends in a population at low risk for this procedure over a 20-year period.In addition to overall cesarean birth risk, cesarean deliveries for nonreassuring fetal status and labor arrest were individually analyzed.Of an estimated 76.7 million delivery hospitalizations, 21.5 million were excluded according to the Society for Maternal-Fetal Medicine definition, and 14.7 million were excluded according to additional criteria. Of the estimated 40 517 867 deliveries included, 12.1% (4 885 716 deliveries) were by cesarean delivery. Cesarean deliveries among patients at low risk for the procedure increased from 9.7% to 13.9% between 2000 and 2009, plateaued, and then decreased from 13.0% to 11.1% between 2012 and 2019. The AAPC for cesarean delivery was 6.4% (95% CI, 5.2% to 7.6%) from 2000 to 2005, 1.2% from 2005 to 2009 (95% CI, -1.2% to 3.7%), and -2.2% from 2009 to 2019 (95% CI, -2.7% to -1.8%). Cesarean delivery for nonreassuring fetal status increased from 3.4% of all deliveries in 2000 to 5.1% in 2019 (AAPC, 2.1%; 95% CI, 1.7% to 2.5%). Cesarean delivery for labor arrest increased from 3.6% in 2000 to a peak of 4.8% in 2009 before decreasing to 2.7% in 2019. Cesarean deliveries for labor arrest increased during the first half of the study (2000-2009) for the active phase (from 1.5% to 2.1%), latent phase (from 1.1% to 1.5%), and second stage (from 0.9% to 1.3%) and then decreased from 2010 to 2019, from 2.1% to 1.7% for the active phase, from 1.5% to 1.2% for the latent phase, and from 1.2% to 0.9% for the second stage.Cesarean deliveries among patients at low risk for cesarean birth appeared to decrease over the latter years of the study period, with cesarean deliveries for labor arrest becoming less common.